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Lab Demonstrates 3-D Printed Tissue, Blood Vessel Implant

Tobacco plants

Tobacco plants (Beeki, Pixabay)

11 Oct. 2021. A biomedical engineering team transplanted into a lab rat synthetic tissue with blood vessels made by three-dimensional printing. Researchers from Technion – Israel Institute of Technology in Haifa reported the developments, using biocompatible 3-D printing inks made by the company Collplant Biotechnologies, last month in the journal Advanced Materials.

A team led by Technion biomedical engineering professor Shulamit Levenberg is seeking better options for clinicians and patients to replace damaged tissue from wounds or burns. Much of today’s replacement tissue is based on collagen derived from human cadavers or animal sources, which increases risks of rejection by the recipients. In addition, replacement tissue needs to contain or support regrowth of blood vessels to provide oxygen and nutrients to the wound or burn site, and support normal tissue functions.

Collplant Biotechnologies, in Rehovot, Israel, develops an engineered form of human collagen called rhCollagen, short for recombinant human collagen. The company makes rhCollagen from tobacco plants genetically engineered with five human genes. While tobacco is associated with harmful health outcomes, it is a fast-growing plant, often studied in labs as a model species. Extracting, processing, and purifying tobacco leaves, says CollPlant, returns a pristine form of human collagen — the most abundant protein in the body found mainly in skin, bones, and and muscles — that performs better and without harmful immune responses than collagen derived from animal and other human tissue.

Printed blood vessels from rhCollagen ink

One method for producing engineered replacement tissue is through 3-D printing. Collplant says its bioprinting inks made from rhCollagen can be used in several types of 3-D printers, such as ink-jet and extrusion, to produce complex scaffolds made for various cell types. The company says its bioprinting inks are already tested in multiple tissue and organ types. In October 2018, Science & Enterprise reported on a licensing deal with Collplant for one of these projects, to produce 3-D printed human lungs for transplant.

Levenberg and colleagues study regenerating human tissue, including engineered tissue that supports formation of blood vessels. In their paper, the Technion team reported on transplanting a 3-D printed tissue flap, a thick piece of tissue including blood vessels into a lab rat. Tissue flaps are used in reconstructive surgery for transferring tissue from one part of the body to another. The researchers used 3-D printing to produce scaffolds to grow new tissue, with inks made from rhCollagen to produce blood vessels. The team implanted the tissue flap and connected the engineered blood vessel to an artery in the rat’s leg. After two weeks, tests show the implanted blood vessels function normally in the rat.

Levenberg notes in a Collplant statement, “The ability to create vascularized tissue constructs using human collagen from modified plants rather than animal collagen is a very promising step towards development of fully lab-grown implantable tissues.” Yehiel Tal, CEO of Collplant adds, “The results of this study further substantiate the vast potential of rhCollagen-based bioinks for use in 3-D bioprinting applications including in-vitro 3-D models and regenerative medicine.”

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